gradual initiation of sulfamethoxazole/trimethoprim as primary pneumocystis carinii pneumonia prophylaxis

Conditions: Pneumonia, Pneumocystis Carinii; HIV Infections

Summary: to determine whether gradual initiation of sulfamethoxazole/trimethoprim (smx/tmp) reduces the incidence of treatment-limiting adverse reactions compared to the routine initiation of the drugs for pneumocystis carinii pneumonia (pcp) prophylaxis in hiv-infected patients. although a number of clinical trials have demonstrated the superiority of smx/tmp for pcp prophylaxis, the incidence of adverse reactions to this medication is high. in a pilot study in which patients were initiated with smx/tmp prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

although a number of clinical trials have demonstrated the superiority of smx/tmp for pcp prophylaxis, the incidence of adverse reactions to this medication is high. in a pilot study in which patients were initiated with smx/tmp prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred. patients are randomized to receive either gradually increasing doses of smx/tmp suspension or routine daily initiation of smx/tmp double strength (ds) tablets for 2 weeks. all patients will then be switched over to receive open-label smx/tmp ds tablets daily for 10 weeks.

Eligibility criteria:
inclusion criteria concurrent medication: allowed if clinically indicated: * recombinant erythropoietin (repo) and g-csf. allowed for symptomatic treatment of mild study drug toxicity: * antipyretics and analgesics (ibuprofen). * antihistamines (diphenhydramine hcl). * terfenadine or astemizole (but not allowed with concomitant antifungal or macrolide use). * systemic steroids. patients must have: * hiv infection. * cd4 count \<= 250 cells/mm3 or history or presence of thrush. * no history of confirmed or probable pneumocystosis. note: * pregnant women are not excluded, but safety issues should be discussed with patient prior to enrollment. * this study is appropriate for prisoner participation. * coenrollment in ongoing actg antiretroviral studies is permitted provided no new study drugs are added to the patient's drug regimen for 4 weeks before or after initiation of smx/tmp. prior medication: allowed: * prior aerosolized pentamidine and dapsone for primary pcp prophylaxis. exclusion criteria co-existing condition: patients with the following symptoms or conditions are excluded: * known adverse reactions to sulfa, trimethoprim, or smx/tmp. * inability to comply with dosing schedule or complete dosing record. concurrent medication: excluded: * procysteine. * glutathione. * n-acetylcysteine (nac). * antihistamines (unless used for symptomatic treatment of study drug toxicity). * systemic corticosteroids (unless used for replacement purposes). * leucovorin calcium (unless used for symptomatic treatment of study drug toxicity). * tmp or sulfa drugs outside of the study. prior medication: excluded at any time: * prior smx/tmp as primary pcp prophylaxis. excluded within 4 weeks prior to study entry: * initiation of antiretroviral agents. * initiation of anti-infective agents (including smx/tmp for another indication). excluded within 2 weeks prior to study entry: * antihistamines. * procysteine. * glutathione. * n-acetylcysteine (nac). * systemic corticosteroids (unless used for replacement purposes). * leucovorin calcium. * tmp and sulfa drugs separately.

Keywords: trimethoprim-sulfamethoxazole combination pneumonia, pneumocystis carinii acquired immunodeficiency syndrome aids-related complex sulfamethoxazole-trimethoprim